American Chemical Society
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Divergent [2 + n] Heteroannulation of β‑CF3‑1,3-enynes with Alkyl Azides via Hydrogen Atom Transfer and Radical Substitution

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journal contribution
posted on 2024-01-22, 13:42 authored by Yu-Zhong Yang, Qi Xue, Zhi-Qiang Xiong, Yang Li, Xuan-Hui Ouyang, Ming Hu, Jin-Heng Li
A copper-promoted divergent intermolecular [2 + n] heteroannulation of β-CF3-1,3-enynes with alkyl azides via alkyl radical-driven HAT and radical substitution (C–C bond formation) to form four- to ten-membered saturated N-heterocycles is developed. This method enables the aryl-induced or kinetically controlled site selective functionalization of the remote C(sp3)–H bonds at positions 2, 3, 4, 5, 6, 7, or 8 toward the nitrogen atom through triplet nitrene formation, radical addition across the CC bond, HAT and radical substitution cascades, and features a broad substrate scope, excellent site selectivity, and facile late-stage derivatization of bioactive molecules. Initial deuterium-labeling and control experiments shed light on the reaction mechanism via nitrene formation and HAT.